Cancedda Ranieri, Mastrogiacomo Maddalena
Emeritus Professor, Università degli Studi di Genova, Genoa, Italy.
Dipartimento di Medicina Interna e Specialità Mediche (DIMI), Università Degli Studi di Genova, Genova, Italy.
Front Bioeng Biotechnol. 2023 May 9;11:1189225. doi: 10.3389/fbioe.2023.1189225. eCollection 2023.
Maintenance of tissue homeostasis and tissue regeneration after an insult are essential functions of adult stem cells (SCs). In adult tissues, SCs proliferate at a very slow rate within "stem cell niches", but, during tissue development and regeneration, before giving rise to differentiated cells, they give rise to multipotent and highly proliferative cells, known as transit-amplifying cells (TACs). Although differences exist in diverse tissues, TACs are not only a transitory phase from SCs to post-mitotic cells, but they also actively control proliferation and number of their ancestor SCs and proliferation and differentiation of their progeny toward tissue specific functional cells. Autocrine signals and negative and positive feedback and feedforward paracrine signals play a major role in these controls. In the present review we will consider the generation and the role played by TACs during development and regeneration of lining epithelia characterized by a high turnover including epidermis and hair follicles, ocular epithelial surfaces, and intestinal mucosa. A comparison between these different tissues will be made. There are some genes and molecular pathways whose expression and activation are common to most TACs regardless their tissue of origin. These include, among others, Wnt, Notch, Hedgehog and BMP pathways. However, the response to these molecular signals can vary in TACs of different tissues. Secondly, we will consider cultured cells derived from tissues of mesodermal origin and widely adopted for cell therapy treatments. These include mesenchymal stem cells and dedifferentiated chondrocytes. The possible correlation between cell dedifferentiation and reversion to a transit amplifying cell stage will be discussed.
维持组织内稳态以及损伤后的组织再生是成体干细胞的重要功能。在成体组织中，成体干细胞在“干细胞龛”内以非常缓慢的速度增殖，但是在组织发育和再生过程中，在产生分化细胞之前，它们会产生多能且高度增殖的细胞，即过渡放大细胞（TACs）。尽管不同组织存在差异，但TACs不仅是从干细胞到有丝分裂后细胞的过渡阶段，它们还积极控制其祖细胞干细胞的增殖和数量，以及其后代向组织特异性功能细胞的增殖和分化。自分泌信号以及正负反馈和前馈旁分泌信号在这些控制中起主要作用。在本综述中，我们将探讨TACs在具有高更新率的衬里上皮（包括表皮和毛囊、眼上皮表面以及肠黏膜）发育和再生过程中的产生及其作用。我们将对这些不同组织进行比较。有一些基因和分子途径，无论其起源组织如何，大多数TACs的表达和激活都是常见的。其中包括Wnt、Notch、Hedgehog和BMP途径等。然而，不同组织的TACs对这些分子信号的反应可能会有所不同。其次，我们将考虑源自中胚层组织且广泛用于细胞治疗的培养细胞。这些包括间充质干细胞和去分化软骨细胞。我们将讨论细胞去分化与恢复到过渡放大细胞阶段之间的可能关联。
